This program focuses on (1) the pathogenesis of the histopathological lesions of Alzheimer type dementia; the neuritic and amyloid plaque and the neurofibrillary tangle and (2) the liklihood that the etiological agent of the disease is a scrapie-like slow virus. The first goal of the program is to isolate and characterize the constituent proteins of the amyloid fibers and the paired helical filaments. By analyzing, ultrastructurally, how specific antisera (both poly and monoclonal) "decorate" these pathological fibers we will determine the candidate protein's contribution to the structure of the fiber and its relationship to other cellular components (eg. cytoskeletal proteins, serum proteins etc.). Our second goal is to develop a living cell model of CNS amyloid formation by isolating and culturing presumptive amyloidogenic cells from areas of the CNS of scrapie mice and Alzheimer brain that are rich in amyloid and amyloid associated cells. The third goal is to attempt to detect the presence of an infectious transmissable agent in Alzheimer brain tissue by examining inoculated mice and hamsters for morphological and "inapparent" changes such as the presence of blood brain barrier alterations and behavioral changes.